Regorafenib plus Nivolumab in Patients with Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)

Shota Fukuoka, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, BPharm Yuichi Mikamoto, Nami Hirano, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Takeshi Kuwata, Yosuke Togashi, Hiroyoshi Nishikawa, Kohei Shitara

Research output: Contribution to journalArticlepeer-review

143 Citations (Scopus)

Abstract

PURPOSE This is a phase Ib trial of regorafenib plus nivolumab for gastric and colorectal cancer. PATIENTS AND METHODS Enrolled patients received regorafenib plus nivolumab in a dose-finding part to estimate the maximum tolerated dose. Additional patients were enrolled in a dose-expansion part. Regorafenib of 80-160 mg was administered once daily for 21 days on/7 days off with nivolumab 3 mg/kg every 2 weeks. The primary end point was dose-limiting toxicity (DLT) during the first 4 weeks to estimate the recommended dose. RESULTS Fifty patients (25 each with gastric and colorectal cancer) were enrolled. All patients had received $ 2 previous lines of chemotherapy, including anti-angiogenetic inhibitors in 96% of patients. Seven patients with gastric cancer had previously been treated with immune checkpoint inhibitors. One patient had microsatellite instability–high colorectal cancer, whereas the remaining patients had microsatellite stable or mismatch repair–proficient tumors. Three DLTs (grade 3 colonic perforation, maculopapular rash, and proteinuria) were observed with regorafenib 160 mg; none were observed with 80 or 120 mg. During the dose-expansion part, regorafenib dose was reduced from 120 to 80 mg because of frequent maculopapular rash. The common grade $ 3 treatment-related adverse events were rash (12%), proteinuria (12%), and palmar-plantar erythrodysesthesia (10%). Objective tumor response was observed in 20 patients (40%), including 11 with gastric cancer (44%) and 9 with colorectal cancer (36%). Median progression-free survival was 5.6 and 7.9 months in patients with gastric and colorectal cancer, respectively. CONCLUSION The combination of regorafenib 80 mg plus nivolumab had a manageable safety profile and encouraging antitumor activity in patients with gastric and colorectal cancer, which warrants additional investigations in larger cohorts.

Original languageEnglish
Pages (from-to)2053-2061
Number of pages9
JournalJournal of Clinical Oncology
Volume38
Issue number18
DOIs
Publication statusPublished - Apr 28 2020
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Regorafenib plus Nivolumab in Patients with Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)'. Together they form a unique fingerprint.

Cite this